At two points during the semester in Organic Chemistry I, students apply the current lecture content to the investigation of molecules of real medicinal value, while also being encouraged to consider various practical aspects of the drug discovery and synthesis pipeline.  Students engage in discussion in small groups and complete worksheets that encourage them to think critically about the design/development and synthesis of organic molecules through the eyes of chemists in the pharmaceutical industry.

Students are encouraged to apply an Entrepreneurial Mindset to approach problems in Organic Chemistry as they relate directly to its application to the design and synthesis of pharmaceuticals.  Through facilitating discussion with their peers, these activities attempt to engage students and help them to:

1. Recognize opportunities to use their Organic Chemistry knowledge in the highly valuable area of drug design and making connections between the course content and real-world applications.

2. See the impact that their designs could have on the behavior of a drug molecule.

3. Create value for themselves in learning to apply chemistry to this practical application and fostering more curiosity in the field.  See how the fundamentals of chemistry they are learning can and have been used to create value for the medical community.

These exercises are designed to facilitate active learning and constructive feedback. The two modules are both implemented in the classroom using the following strategy:

-Students receive an introduction to the process of the drug discovery process and the relevant topic for the given module (either drug design and activity or scale-up synthesis of drug molecules for manufacturing).

-Students are provided a worksheet to work through via discussion of those questions with their tables.  Instructors and TA's walk around the room and facilitate discussion, answer questions, and provide feedback to students' though processes and answers.

-After some time, the instructor reconvenes the class and goes over the key ideas and answers for the worksheet.

Ideally, these exercises serve to introduce students to applying an Entrepreneurial mindset to approaching scientific problems, while also providing review of and practice with course content.

Module 1: "Medicinal Chemistry: Chemical Structure and Drug Design"

The first module is focused on putting the students in the shoes of a medicinal chemist, tasked with designing the structure of a drug to treat a specific target.  This exercise is provided to students following review of general chemistry principles and of drawing and interpreting organic structures. Students use their newly gained knowledge of organic compound structures to connect structural motifs with their biological activity.  They are also encouraged to brainstorm on practical aspects of drug design, focused on how the drug would behave in the body (e.g. selectivity, aqueous solubility, bodily absorption and distribution, metabolism).  The main goals of this exercise are to encourage students to look at organic structures more closely, to practice drawing organic structures themselves, and to spark curiosity in organic chemistry as it relates directly to the field of medicine.

Features of this worksheet and activity include:

1. Exploring the practical considerations for designing an effective drug from the viewpoint of a medicinal chemistry, thinking beyond just the drug binding to the target (e.g. selectivity/side-effects, aqueous solubility, bodily absorption and distribution, metabolism).

2. Integrating knowledge of structural motifs in a series of benzodiazepine structures to determine which are key to their function and which can be independently modified.

3. Combining their newly gained structural knowledge and their own creativity to create their own benzodiazepine structural design that would be expected to be biologically active.

4. Making connections between similar structure and similar biological activity via matching structures of highly prescribed pharmaceuticals that are used to treat similar diseases.

Following this exercise, the instructor gathers responses from students, fills in any missing information, and provides more detail of how drugs behave in the body and why their structural motifs are important for their bioavailability and target selectivity, using pharmacodynamic data and crystal structures from the scientific literature. 

Module 2: "Pharmaceutical Synthesis and Scale-Up"

The second module is focused on putting the students in the shoes of a process chemist, tasked with developing and optimizing a final synthetic route for scale-up production of an approved drug. This exercise is provided to students following in-depth discussion of reactions and synthetic schemes in the course content.  Students use their newly gained knowledge of reactions and combining reactions to create value-added products to explore the synthetic sequences (on paper) and the real-world considerations (in the lab and the plant) through which these compounds are made. 

Features of this worksheet and activity include:

1. Exploring the practical considerations for synthesizing a drug molecule, including reaction efficiency from both economic and environmental standpoints.

2. Making connections between reactions they have recently learned and their application to the synthesis of complex compounds with pharmaceutical applications.

3. Connecting the idea of chirality with increased target selectivity, but increased synthetic complexity.

Following this exercise, the instructor gathers responses from students regarding practical considerations for scale-up synthesis from both chemistry and business perspectives, filling in gaps as needed.  The instructor then goes over the the answers to the reaction questions on the worksheet.  The instructor emphasizes that despite the molecules being complex, the reactions used to make them are the exact same ones they are learning in lecture.  This last point helps connect the material they are learning directly to their recorded application to pharmaceutical compounds that they know.